Abstract
N-CoR and SMRT are corepressor paralogs that partner with and mediate transcriptional repression by a wide variety of metazoan transcription factors, including nuclear hormone receptors. Although encoded by distinct genetic loci, N-CoR and SMRT share substantial sequence interrelatedness, form analogous assemblies with histone deacetylases and auxiliary factors, can interact with overlapping sets of transcription factor partners, and exert overlapping functions in cells. SMRT is subject to negative regulation by MAPK signaling pathways operating downstream of growth factor and stress signaling pathways. We report here that whereas activation of MEKK1 leads to phosphorylation of SMRT, its dissociation from its transcription factor partners in vivo and in vitro, and its redistribution from the cell nucleus to a cytoplasmic compartment, N-CoR is refractory to all these forms of regulation. In contrast to this MAPK cascade, other signal transduction pathways operating downstream of growth factor/cytokine receptors appear able to affect both corepressor paralogs. Our results indicate that SMRT and N-CoR are embedded in distinct regulatory networks and that the two corepressors interpret growth factor, cytokine, differentiation, and prosurvival signals differently.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 54676-54686 |
| Number of pages | 11 |
| Journal | Journal of Biological Chemistry |
| Volume | 279 |
| Issue number | 52 |
| DOIs | |
| State | Published - Dec 24 2004 |
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ASJC Scopus subject areas
- Biochemistry
Cite this
SMRT and N-CoR corepressors are regulated by distinct kinase signaling pathways. / Jonas, Brian; Privalsky, Martin L.
In: Journal of Biological Chemistry, Vol. 279, No. 52, 24.12.2004, p. 54676-54686.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - SMRT and N-CoR corepressors are regulated by distinct kinase signaling pathways
AU - Jonas, Brian
AU - Privalsky, Martin L.
PY - 2004/12/24
Y1 - 2004/12/24
N2 - N-CoR and SMRT are corepressor paralogs that partner with and mediate transcriptional repression by a wide variety of metazoan transcription factors, including nuclear hormone receptors. Although encoded by distinct genetic loci, N-CoR and SMRT share substantial sequence interrelatedness, form analogous assemblies with histone deacetylases and auxiliary factors, can interact with overlapping sets of transcription factor partners, and exert overlapping functions in cells. SMRT is subject to negative regulation by MAPK signaling pathways operating downstream of growth factor and stress signaling pathways. We report here that whereas activation of MEKK1 leads to phosphorylation of SMRT, its dissociation from its transcription factor partners in vivo and in vitro, and its redistribution from the cell nucleus to a cytoplasmic compartment, N-CoR is refractory to all these forms of regulation. In contrast to this MAPK cascade, other signal transduction pathways operating downstream of growth factor/cytokine receptors appear able to affect both corepressor paralogs. Our results indicate that SMRT and N-CoR are embedded in distinct regulatory networks and that the two corepressors interpret growth factor, cytokine, differentiation, and prosurvival signals differently.
AB - N-CoR and SMRT are corepressor paralogs that partner with and mediate transcriptional repression by a wide variety of metazoan transcription factors, including nuclear hormone receptors. Although encoded by distinct genetic loci, N-CoR and SMRT share substantial sequence interrelatedness, form analogous assemblies with histone deacetylases and auxiliary factors, can interact with overlapping sets of transcription factor partners, and exert overlapping functions in cells. SMRT is subject to negative regulation by MAPK signaling pathways operating downstream of growth factor and stress signaling pathways. We report here that whereas activation of MEKK1 leads to phosphorylation of SMRT, its dissociation from its transcription factor partners in vivo and in vitro, and its redistribution from the cell nucleus to a cytoplasmic compartment, N-CoR is refractory to all these forms of regulation. In contrast to this MAPK cascade, other signal transduction pathways operating downstream of growth factor/cytokine receptors appear able to affect both corepressor paralogs. Our results indicate that SMRT and N-CoR are embedded in distinct regulatory networks and that the two corepressors interpret growth factor, cytokine, differentiation, and prosurvival signals differently.
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U2 - 10.1074/jbc.M410128200
DO - 10.1074/jbc.M410128200
M3 - Article
VL - 279
SP - 54676
EP - 54686
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 52
ER -